Department of Biosciences and Bioengineering, Indian Institute of Technology, Bombay, Powai, India.
Molecular Biology & Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Mol Microbiol. 2021 Oct;116(4):1079-1098. doi: 10.1111/mmi.14796. Epub 2021 Aug 30.
Shugoshin proteins are evolutionarily conserved across eukaryotes, with some species-specific cellular functions, ensuring the fidelity of chromosome segregation. They act as adaptors at various subcellular locales to mediate several protein-protein interactions in a spatio-temporal manner. Here, we characterize shugoshin (Sgo1) in the human fungal pathogen Candida albicans. We observe that Sgo1 retains its centromeric localization and performs its conserved functions of regulating the sister chromatid biorientation, centromeric condensin localization, and maintenance of chromosomal passenger complex (CPC). We identify novel roles of Sgo1 as a spindle assembly checkpoint (SAC) component with functions in maintaining a prolonged SAC response by retaining Mad2 and Bub1 at the kinetochores in response to improper kinetochore-microtubule attachments. Strikingly, we discover the in vivo localization of Sgo1 along the length of the mitotic spindle. Our results indicate that Sgo1 performs a hitherto unknown function of facilitating timely disassembly of the mitotic spindle in C. albicans. To summarize, this study unravels a unique functional adaptation of shugoshin in maintaining genomic stability.
着丝粒蛋白在真核生物中具有进化保守性，具有一些物种特异性的细胞功能，确保了染色体分离的保真度。它们作为衔接蛋白在各种亚细胞位置发挥作用，以时空方式介导几种蛋白质-蛋白质相互作用。在这里，我们对人类真菌病原体白色念珠菌中的着丝粒蛋白（Sgo1）进行了表征。我们观察到 Sgo1 保留其着丝粒定位，并发挥其保守功能，调节姐妹染色单体的双取向、着丝粒凝聚素的定位以及染色体乘客复合物（CPC）的维持。我们确定了 Sgo1 的新作用，作为纺锤体组装检查点（SAC）的组成部分，其功能是通过在动粒上保留 Mad2 和 Bub1 来维持延长的 SAC 反应，以响应不正确的动粒-微管附着。引人注目的是，我们发现 Sgo1 在有丝分裂纺锤体的长度上进行体内定位。我们的结果表明，Sgo1 在白色念珠菌中执行了一个迄今为止未知的功能，即促进有丝分裂纺锤体的及时解体。总之，这项研究揭示了着丝粒蛋白在维持基因组稳定性方面的独特功能适应性。
